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Depression and subsequent risk for incident rheumatoid arthritis among women


Arthritis Care Res (Hoboken). 2020 Sep 16.doi: 10.1002/acr.24441. Online ahead of print.

Jeffrey A Sparks 1 2, Susan Malspeis 1, Jill Hahn 1 2, Jiaqi Wang 1, Andrea L Roberts 3, Laura D Kubzansky 2 3, Karen H Costenbader 1 2

Author Information

1 Brigham and Women's Hospital, Boston, MA, United States.

2 Harvard Medical School, Boston, MA, United States.

3 Harvard T.H. Chan School of Public Health, Boston, MA, United States.


Objective: We investigated the association of depression with subsequent risk of rheumatoid arthritis (RA) by serologic phenotype.

Methods: We performed a cohort study using pooled data from the Nurses' Health Study (NHS, 1992-2014) and NHSII (1993-2015). Depression was defined using a composite definition: clinician diagnosis, regular antidepressant use, or Mental Health Inventory-5 score <60 by time-updated questionnaires during follow-up. Incident RA cases met research criteria by medical review. Covariates, including smoking, diet, and body mass index, were obtained by questionnaires. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for RA (overall and by serologic phenotype) according to depression status, adjusted for potential confounders. All analyses included a time separation between assessments of depression and the window for RA risk of at least 4 years to lower the possibility that depressive symptoms due to early RA symptoms prior to diagnosis explained any associations.

Results: Among 195,358 women, we identified 858 incident RA cases (65% seropositive) over 3,087,556 person-years (median 17.9 years/participant). Compared to women without depression, those with depression had multivariable HRs (95%CIs) of: 1.28(1.10-1.48) for all RA; 1.12(0.93-1.35) for seropositive RA; and 1.63(1.27-2.09) for seronegative RA. When analyzing components of the composite depression exposure variable, regular antidepressant use was not associated with subsequent seropositive RA (HR 1.21, 95%CI 0.97-1.49) and was associated with seronegative RA (HR 1.75, 95%CI 1.32-2.32).

Conclusion: Indicators of depression, specifically antidepressant use, were associated with subsequent increased risk for seronegative RA, and this finding was not explained by measured lifestyle factors prior to clinical presentation.